A three-drug combination with panobinostat significantly increased median progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma. Adding panobinostat to the multiple myeloma treatment armamentarium could help extend the benefit of standard-of-care therapy, according to results from the PANORAMA1 trial published in Lancet Oncology.

Multiple myeloma is an incurable disease, with, unfortunately, a large portion of patients relapsing or becoming resistant to treatment, Jesús San-Miguel, MD, lead investigator on the study, noted — underscoring the need for new therapies with novel mechanisms of action to manage the disease and improve outcomes.

Panobinostat, a potent oral pandeacetylase inhibitor, has demonstrated synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. In the current study, Dr. San-Miguel and colleagues compared the efficacy of panobinostat and placebo when added to the standard two-drug regimen of bortezomib + dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma.

All 768 patients in the multicenter, randomized, placebo-controlled, doubleblind, phase III PANORAMA1 trial had relapsed or relapsed/refractory multiple myeloma and had received between one and three previous treatment regimens. Patients were randomly assigned to receive 21-day cycles of either placebo or panobinostat (20 mg), in combination with bortezomib (1.3 mg/m2) and dexamethasone (20 mg).

The 387 patients who received panobinostat were followed for a median of 6.47 months, while the 381 patients who received placebo were followed for a median of 5.59 months.

While overall response rates did not differ between the groups, the addition of panobinostat did lead to clinically meaningful increases in complete and near-complete response rates and duration of response.

Data on overall survival data – the study’s key secondary endpoint – are not yet mature, the authors noted. However, at the time of this analysis, median overall survival was greater in the panobinostat group: 33.64 months compared with 30.39 months.

Serious adverse events were reported in 228 (60%) of 381 patients in the panobinostat group and 157 (42%) of 377 patients in the placebo group. The most common grade 3-4 events in the panobinostat arm included thrombocytopenia, lymphopenia, and neutropenia. Adverse events, the authors noted, were generally manageable through supportive care and dose reductions.

“Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed/ refractory multiple myeloma,” the authors concluded, but added that longer follow-up is necessary to determine whether there is any effect on overall survival.